Borna disease is a neurological disease of horses and sheep characterized by acute encephalitis accompanied by motor abnormalities and chronic neurological deficits. Borna disease has long been known to be infectious and experimentally transmissible to a large number of species ranging from primates to rodents. The symptoms of disease in experimentally infected animals range from subtle changes in behavior to major neurological deficits. These differences in disease depend on the species infected and whether there is a persistent tolerant infection or an immunopathological process. The etiologic agent (i.e. virus) of Borna disease has not been definitively identified. However, cell-free Borna disease virus (BDV) has been isolated from a productive cell culture system developed in this laboratory. In addition, the recent isolation of cDNA clones specific for the Borna disease virus (BDV) has provided molecular probes to identify Borna specific RNAs in infected cells and has aided in the characterization of the BDV RNA isolated from virions as negative- stranded. The overlapping cDNA clones isolated in this laboratory identified four mRNAs (3.6, 2.1, 1.4 and O.85kb) as well as large positive and negative-stranded RNAs of lO.5kb. These clones encode the 14,24, and 38kD proteins which are present both in infected cells and in virions. These cDNA clones are overlapping with common ends, 3' leading to the deduction of the gene order as 5' 38kD, l4kD, 24kD 3' in the positive- sense orientation. All these data suggest this virus is unique in its biology and in its genomic organization. With the establishment of a cell culture system and the availability of molecular clones, we have the tools for characterizing this unique virus. BDV may represent a new family of viruses and be a model system for examining the biochemical basis for behavioral/neurological diseases. Borna disease virus will be purified from our productive cell culture system. Virion proteins will be characterized and genomic (negative- strand) RNA will be isolated for characterization and molecular cloning. Studies in this proposal will isolate cDNA clones for all the BDV specific mRNAs, and sequence the genomic RNA. Analysis of the cDNA clones from genomic and mRNAs will be used to determine the gene order and the organization of the mRNAs in relation to the viral genome.